Informed consent and assent guide for paediatric clinical trials in Europe.

OBJECTIVE: Clinical trial sponsors spend considerable resources preparing informed consent (IC) and assent documentation for multinational paediatric clinical trial applications in Europe due to the limited and dispersed patient populations, the variation of national legal and ethical requirements, and the lack of detailed guidance. The aim of this study was to design new easy-to-use guide publicly available on European Medicines Agency's, Enpr-EMA website for all stakeholders. METHODS: Current EU legal, ethical and regulatory guidance for paediatric clinical trials were collated, analysed and divided into 30 subject elements in two tables. The European Network of Young Person's Advisory Group reviewed the data and provided specific comments. A three-level recommendation using 'traffic light' symbols was designed for four age groups of children, according to relevance and the requirements. RESULTS: A single guide document includes two tables: (1) general information and (2) trial-specific information. In the age group of 6-9 years old, 92% of the trial-specific subject elements can be or should be included in the IC discussion. Even in the youngest possible age group (2-5 years old children), the number of elements considered was, on average, 52%. CONCLUSION: The EU Clinical Trial Regulation (2014) does not contain specific requirements exclusively for paediatric clinical trials. This work is the first to extensively collate all the current legal, regulatory and ethical documentation on the IC process, together with input from adolescents. This guide may increase the ethical standards in paediatric clinical trials.

Correction to: How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement.

The article How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement, written by Thomas Severin et al. was originally published electronically on the publisher's internet portal on February 6, 2020 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on April 22, 2020 to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement.

BACKGROUND: Pediatric regulations enacted in both Europe and the USA have disrupted the pharmaceutical industry, challenging business and drug development processes, and organizational structures. Over the last decade, with science and innovation evolving, industry has moved from a reactive to a proactive mode, investing in building appropriate structures and capabilities as part of their business strategy to better tackle the challenges and opportunities of pediatric drug development. METHODS: The EFGCP Children's Medicines Working Party and the IQ Pediatric working group have joined their efforts to survey their member company representatives to understand how pharmaceutical companies are organized to fulfill their regulatory obligations and optimize their pediatric drug development programs. RESULTS: Key success factors and recommendations for a fit-for-purpose Pediatric Expert Group (PEG) were identified. CONCLUSION: Pediatric structures and expert groups were shown to be important to support optimization of the development of pediatric medicines.

Does the EU's Paediatric Regulation work for new medicines for children in Denmark, Finland, Norway and Sweden? A cross-sectional study.

OBJECTIVE: The aim of this study was to assess the marketing status of the new paediatric medicinal products listed in the 10-year report as initially authorised between 2007 and 2016, reflecting the product availability in four Nordic countries. DESIGN: This is a cross-sectional study. SETTING: Analysis of the national medicine agency's databases in Denmark, Finland, Norway and Sweden. DATA SOURCE: New medicinal products with paediatric indications and new paediatric formulations listed in the Annex of European Medicines Agency's EU Paediatric Regulation 10-year report. DATA ANALYSIS: The products were classified according to national marketing status between January 2019 and March 2019, whether a product was authorised and whether the product was marketed. MAIN OUTCOME MEASURES: The percentages of the new medicinal products with paediatric indications and new paediatric formulations having a valid marketing authorisation and being marketed, both in terms of the sums of all countries and separately for each country. RESULTS: Across the four countries, 21%-32% (16/76-24/76) of the new medicinal products were not marketed. Of the new formulations relevant to children, 29%-50% (16/56-28/56) were not marketed, and a significant proportion of these products had never been marketed. CONCLUSIONS: This study reflects the reality of the implementation of the Paediatric Regulation. The results show that several new paediatric medicines and new formulations are not marketed. This affects the product availability. Similar data from other countries are needed to evaluate the overall European status to find remedies to current situation and increase the availability of the medicines for children.

Investigating the roles and training of paediatric research nurses working across Europe: a questionnaire-based survey.

BACKGROUND: The key role played by research nurses in coordinating clinical trials in a paediatric setting has developed in line with increasing complexities of trial design. A questionnaire-based survey was conducted to investigate the training of research nurses involved in paediatric trials across Europe, to identify potential training needs and compare roles across specialties and countries. METHODS: A structured, cross-sectional questionnaire survey was used, with the aim of describing and quantifying research nurse experiences. The questionnaire was designed to cover four main areas of interest: demographics, training, clinical trial experience and research nurse roles/activities. RESULTS: The questionnaire was completed by 341 respondents across 45 different specialties in 20 European countries. A higher percentage of research nurses within 3 years of taking up post were dissatisfied with the level of training received (16%), as compared with those in post for 3-6 years (8%) and >6 years (6%). There was a trend towards a higher percentage of respondents receiving self-funded training in mainland Europe, with reported values of 15%-20%, as compared with <5% in the UK and Ireland. Only 3% of research nurses prescribed investigational medicinal products in a clinical trial setting, with contrasting roles observed between countries. CONCLUSIONS: While high levels of training satisfaction were observed, 67% of respondents felt they would benefit from additional training in line with frequently changing practices. Currently, low levels of nurse prescribing are observed in a paediatric clinical trial setting across Europe. Appropriate research nurse training programmes should be promoted through national networks across Europe.

Informed consent for paediatric clinical trials in Europe.

OBJECTIVE: Paediatric clinical trials are often conducted as multinational trials. Informed consent or assent is part of the ethics committee approval for clinical trials. The consent requirements vary between countries due to national laws and regulations, which are not harmonised in Europe. These discrepancies can present challenges for paediatric clinical trials. The aim of this study was to assemble these consent and assent requirements across the European Economic Area. The collated national requirements have not been publicly available before, despite a real need for this data. METHODS: National consent and assent requirements for paediatric clinical trials were analysed and collated for 25 European Union Member States and 2 European Free Trade Association countries until the end of 2014. The data were retrieved from existing databases and through communication with the competent authorities and selected ethics committees. Results from a literature search for international or national guidelines, declarations and conventions and academic societies' publications served as comparison material. RESULTS: Consent and assent requirements are heterogeneous across these countries. We compiled our findings in 'The Informed Consent and Assent Tool Kit', a table including 27 national consent and assent requirements listed by individual country. CONCLUSIONS: Wide variation in paediatric consents and assents presents challenges for multinational paediatric trials in Europe. The toolkit is available for all those involved in paediatric clinical trials and ethics committees, providing a new platform for proactive feedback on informed consent requirements, and may finally lead to a needed harmonisation process, including uniform standards accepted across Europe.

Limited impact of EU paediatric regulation on Finnish clinical trials highlights need for Nordic collaboration.

UNLABELLED: The Finnish Investigators Network for Paediatric Medicines (FINPEDMED) was established in 2007, to meet the expected increase in paediatric clinical trials following the new EU Paediatric Regulation. Between 2007 and 2012, FINPEDMED received 91 trial requests, 18 trials were started, and in 24 cases, Finnish investigators were not selected by sponsors. CONCLUSION: This experience from Finland highlights the need for Nordic collaboration to increase expertise, recruitment base and attractiveness for sponsors.